Virtual screening of small natural compounds against NS1 protein of DENV, YFV and ZIKV

Abstract

Diseases caused by viruses of the genus Flavivirus are among the main diseases that affect the world and they are a serious public health problem. Three of them stand out: Dengue, Yellow fever and Zika viruses. The non-structural protein 1 (NS1), encoded by this viral genus, in its dimeric form, plays important roles in the pathogenesis and RNA replication of these viruses. Therefore, the identification of chemicals with the potential to inhibit the formation of the NS1 protein dimer of DENV, YFV and ZIKV would enable them to act as a multi-target drug. For this, we selected conformations of the NS1 protein monomer with similar β-roll domain structure among the three virus species from conformations obtained from molecular dynamics simulations performed in GROMACS in 5 replicates of 150 ns for each species. After selecting the protein structures, a virtual screening of compounds from the natural products catalog of the ZINC database was performed using AutoDock Vina. The 100 best compounds were classified according efficiency criteria. Two compounds were observed in common to the species, with energy scores ranging from −9.2 kcal/mol to −10.1 kcal/mol. The results obtained here demonstrate the high similarity of NS1 proteins in the Flavivirus genus and high affinity for the same compounds; thus justifying the potential of these small molecules act in multitarget therapy.

Communicated by Ramaswamy H. Sarma

Keywords:

• Computational biology
• Flavivirus
• molecular docking
• molecular dynamics
• rational drug design

Acknowledgements

This work, performed at Universidade Federal de Goiás, was supported by the Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI/CNPq), Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Additionally, G.L.M. was supported by fellowships from CAPES. MVS was supported by fellowships from Fundação de Amparo à Pesquisa Do Estado de São Paulo Research Foundation (FAPESP) São Paulo Number 2020/12875‐5

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Protocol designed by GLM and RAS.

Monitoring the execution of work RAS.

Methodology performed by GLM and RAS.

Manuscript was written and reviewed by GLM, RAS, MVS and MLN.

Additional information

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq): http://dx.doi.org/10.13039/501100003593. Fundação de Amparo á Pesquisa do Estado de Goiás: http://dx.doi.org/10.13039/501100005285. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES): http://dx.doi.org/10.13039/501100002322. Fundação de Amparo á Pesquisa do Estado de São Paulo (FAPESP): http://dx.doi.org/10.13039/501100001807.